CurrentColorado Rocky Mountain Health PlansPolicy 2025D0072N

RNA-Targeted Therapies (Amvuttra and Onpattro)

Defines medical necessity criteria, initial and continuation authorization rules, exclusions, and applicable billing codes for Amvuttra (vutrisiran) and Onpattro (patisiran) for treatment of cardiomyopathy (wtATTR and hATTR) and polyneuropathy (hATTR). Also notes CMS applicability and coding references.

Policy Summary

PayerColorado Rocky Mountain Health Plans

PolicyRNA-Targeted Therapies (Amvuttra and Onpattro)

Policy CodePolicy 2025D0072N

Change TypeCoverage criteria added for Amvuttra in ATTR-CM; codes updated

Effective DateJun 1, 2025

Next Review Date

Key ActionSubmit prior authorization with required diagnostic proof and baseline/ongoing clinical measures; authorizations limited to ≤12 months and prescriber specialty requirements apply.

POLICY UPDATE CHANGES

06/01/2025: Removed language indicating Amvuttra and Onpattro are unproven and not medically necessary for ATTR-CM and added coverage criteria indicating Amvuttra is proven and medically necessary for ATTR-CM when criteria are met.

Added ICD-10 diagnosis codes E85.0, E85.4, and E85.82 to applicable codes.

07/01/2025: Template update and Benefit Considerations update.

08/15/2025: Corrected typographical error.

2Drugs discussed (Amvuttra, Onpattro)

4Applicable ICD-10 codes listed

12Maximum months per authorization

3Clinical severity thresholds listed

Coverage Summary

Scope: This policy defines medical necessity criteria, initial and continuation authorization rules, exclusions, and applicable billing codes for Amvuttra (vutrisiran) and Onpattro (patisiran) for treatment of cardiomyopathy (wtATTR and hATTR) and polyneuropathy (hATTR). Coverage stance is mixed, with Amvuttra described as proven and medically necessary for ATTR cardiomyopathy when all criteria are met and both agents proven and medically necessary for hATTR polyneuropathy when criteria are met. Drugs discussed: Amvuttra (vutrisiran) and Onpattro (patisiran). High-level authorization rules: initial and continuation approvals require documentation of diagnosis, baseline and ongoing clinical measures, prescriber specialty requirements (cardiology for cardiomyopathy, neurology for polyneuropathy), combination-therapy exclusions, dosing per FDA label, and authorizations are limited to no more than 12 months for both initial and continuation periods.

Initial Therapy — Amvuttra for ATTR‑CM

Amvuttra (vutrisiran) for cardiomyopathy (wtATTR or hATTR) - Initial Therapy

Medically necessary when ALL of the following are met:

ALL of the following

Diagnosis of wild-type or hereditary ATTR-mediated amyloidosis with cardiomyopathy (ATTR-CM)
Documentation of one of the following
- The patient has a pathogenic TTR mutation (e.g., V30M)
- Cardiac or noncardiac tissue biopsy demonstrating histologic confirmation of ATTR amyloid deposits
- OR imaging pathway: All of the following: Echocardiogram or cardiac magnetic resonance imaging suggestive of amyloidosis; Radionuclide imaging showing grade 2 or 3 cardiac uptake; Absence of light chain amyloidosis
  May require prior authorization and notification
Patient has New York Heart Association (NYHA) Functional Class I, II, or III heart failure
Physician attests that the patient has an NT-proBNP level that, when combined with signs and symptoms, is considered definitive for a diagnosis of ATTR-CM
Documentation of one of the following clinical course criteria
- History of heart failure, with at least one prior hospitalization for heart failure
- Presence of signs and symptoms of heart failure (e.g., dyspnea, edema)
One of the following background therapy/hospitalization/intolerance criteria
- Documentation of progressive worsening or an event resulting in hospitalization related to hATTR-mediated amyloidosis with cardiomyopathy (ATTR-CM) while on one of the following: Vyndaqel (tafamidis meglumine) or Vyndamax (tafamidis); or Attruby (acoramidis)
- Documentation of intolerance or contraindication to both of the following: Vyndaqel (tafamidis meglumine) or Vyndamax (tafamidis); and Attruby (acoramidis)
Patient is not receiving Amvuttra in combination with RNA interference agents (e.g., Onpattro/patisiran, Wainua/eplontersen, Tegsedi/inotersen)
Patient is not receiving Amvuttra in combination with transthyretin stabilizers (e.g., Vyndaqel or Vyndamax/tafamidis)
Prescribed by or in consultation with a cardiologist
Dosing is in accordance with the FDA prescribing information
Initial authorization is for no more than 12 months

Continuation Therapy — Amvuttra for ATTR‑CM

Amvuttra (vutrisiran) for cardiomyopathy (wtATTR or hATTR) - Continuation of Therapy

Medically necessary when ALL of the following are met:

ALL of the following

Patient has previously received treatment with Amvuttra for wtATTR or hATTR amyloidosis
Documentation that the patient has experienced a positive clinical response to Amvuttra (e.g., improved symptoms, quality of life, slowing of disease progression, decreased hospitalizations, etc.)
Documentation that the patient continues to have NYHA Functional Class I, II, or III heart failure
Patient is not receiving Amvuttra in combination with RNA interference agents (e.g., Onpattro/patisiran, Wainua/eplontersen, Tegsedi/inotersen)

Initial Therapy — hATTR Polyneuropathy (Amvuttra, Onpattro)

Amvuttra (vutrisiran) and Onpattro (patisiran) for polyneuropathy of hATTR - Initial Therapy

Medically necessary when ALL of the following are met:

ALL of the following

Diagnosis of hATTR amyloidosis with polyneuropathy
Documentation that the patient has a pathogenic TTR mutation (e.g., V30M)
Documentation of one baseline severity / performance measure
- Patient has a baseline polyneuropathy disability (PND) score ≤ IIIb≤ IIIb

Continuation Therapy — hATTR Polyneuropathy (Amvuttra, Onpattro)

Amvuttra (vutrisiran) and Onpattro (patisiran) for polyneuropathy of hATTR - Continuation of Therapy

Medically necessary when ALL of the following are met:

ALL of the following

Patient has previously received treatment with Amvuttra or Onpattro
Ongoing severity/performance criterion
- Patient continues to have a PND score ≤ IIIb≤ IIIb
- Patient continues to have a FAP stage 1 or 2Stage 1 or 2

Not Medically Necessary / Unproven

Amvuttra and Onpattro are unproven and not medically necessary for the following:

ANY of the following

Sensorimotor or autonomic neuropathy not related to hATTR amyloidosis
Primary or leptomeningeal amyloidosis

Applicable Codes

HCPCS / J-codes (drug administration units)HCPCS

J0222	Injection, patisiran, 0.1 mg
J0225	Injection, vutrisiran, 1 mg

ICD-10 Diagnosis Codes (applicable)ICD-10

E85.0	Non-neuropathic heredofamilial amyloidosis
E85.1	Neuropathic heredofamilial amyloidosis
E85.4	Organ-limited amyloidosis
E85.82	Wild-type transthyretin-related (ATTR) amyloidosis

Provider Actions & Billing Impact

Prior Authorization

Prior authorization required

Initial and continuation authorizations are limited to no more than 12 months and may require prior authorization/notification for radionuclide imaging uptake documentation; prescriber specialty requirements apply (cardiologist for cardiomyopathy, neurologist for polyneuropathy).

J0222
J0225

Documentation Required

Clinical documentation requirements

For approval, submit diagnostic proof and baseline/ongoing clinical measures to support medical necessity and continuation. Required documentation includes genetic or tissue confirmation or specified imaging with exclusion of light-chain (AL) amyloidosis; baseline and ongoing measures of neurologic and functional status; cardiac measures and hospitalization history; and evidence of positive response for continuation.

Clinical Evidence

0.72HELIOS-B (vutrisiran) HR for death/recurrent CV events

mNIS+7 / QoLAPOLLO (patisiran): improved mNIS+7 and Norfolk QoL; significant reduction in neuropathy progression

-17.0Vutrisiran polyneuropathy study mNIS+7 LS mean difference vs external placebo (Month 9)

Key pivotal evidence: HELIOS-B (vutrisiran) was a phase 3 trial that reduced the composite of death and recurrent cardiovascular events (HR 0.72; 95% CI 0.56–0.93; p=0.01). APOLLO (patisiran) was a phase 3 trial that improved neuropathy measures (mNIS+7) and Norfolk QoL scores, demonstrating significant reductions in neuropathy progression. A phase 3 vutrisiran polyneuropathy study showed an mNIS+7 least-squares mean difference of -17.0 versus external placebo (p<0.001), with associated improvements in quality-of-life measures.

Background

Background: Amvuttra (vutrisiran) and Onpattro (patisiran) are double-stranded small interfering RNAs (siRNAs) that target transthyretin (TTR) mRNA to degrade it and reduce circulating TTR and tissue amyloid deposits; they are formulated to direct activity to the liver, the primary source of circulating TTR. FDA-approved indications: patisiran is indicated for the polyneuropathy of hereditary transthyretin-mediated (hATTR) amyloidosis in adults; vutrisiran is indicated for the polyneuropathy of hATTR amyloidosis in adults and for cardiomyopathy of wild-type or hereditary ATTR in adults to reduce cardiovascular mortality, cardiovascular hospitalizations, and urgent heart failure visits.

Definitions: ATTR-CM = Transthyretin-mediated amyloidosis with cardiomyopathy; PND = Polyneuropathy Disability score; NIS = Neuropathy Impairment Score; KPS = Karnofsky Performance Status; NYHA = New York Heart Association Functional Classification.

Revision History

06/01/2025policy_revisionLatest

Removed prior language stating Amvuttra and Onpattro were unproven and not medically necessary for ATTR-CM; added coverage rationale and detailed initial and continuation criteria establishing Amvuttra (vutrisiran) as proven and medically necessary for treatment of wild-type or hereditary ATTR cardiomyopathy when specified criteria are met (diagnosis, biopsy/genetic or imaging evidence including radionuclide grade 2–3 uptake, NYHA I–III, NT‑proBNP documentation, prior HF hospitalization or signs/symptoms, background therapy/hospitalization or intolerance rules, noncombination rules, cardiologist prescriber, FDA dosing, initial/continuation authorization up to 12 months).

07/01/2025administrative_update

Template update and Benefit Considerations updated.

Policy Summary

PayerColorado Rocky Mountain Health Plans

PolicyRNA-Targeted Therapies (Amvuttra and Onpattro)

Policy CodePolicy 2025D0072N

Change TypeCoverage criteria added for Amvuttra in ATTR-CM; codes updated

Effective DateJun 1, 2025

Next Review Date

Key ActionSubmit prior authorization with required diagnostic proof and baseline/ongoing clinical measures; authorizations limited to ≤12 months and prescriber specialty requirements apply.

On This Page

Patient is not receiving Amvuttra in combination with transthyretin stabilizers (e.g., Vyndaqel or Vyndamax/tafamidis)

Prescribed by or in consultation with a cardiologist

Dosing is in accordance with the FDA prescribing information

Authorization is for no more than 12 months

Patient has a baseline familial amyloid polyneuropathy (FAP) Stage 1 or 2Stage 1 or 2

Patient has a baseline neuropathy impairment score (NIS) ≥ 5 and ≤ 130≥ 5 and ≤ 130

Patient has a baseline Karnofsky performance status (KPS) score ≥ 60%≥ 60%

Presence of clinical signs and symptoms of the disease (e.g., peripheral sensorimotor polyneuropathy, autonomic neuropathy, motor disability, etc.)

Patient has not had a liver transplant

Combination therapy exclusion (drug-specific)

For Amvuttra, patient is not receiving Amvuttra in combination with any of: RNA interference agents (e.g., Onpattro/patisiran, Wainua/eplontersen, Tegsedi/inotersen) or transthyretin stabilizers (e.g., Vyndaqel/Vyndamax)
For Onpattro, patient is not receiving Onpattro in combination with any of: RNA interference agents (e.g., Amvuttra/vutrisiran, Wainua/eplontersen, Tegsedi/inotersen) or transthyretin stabilizers (e.g., Vyndaqel/Vyndamax)

Prescribed by or in consultation with a neurologist

Dosing is in accordance with the FDA prescribing information

Initial authorization is for no more than 12 months

Patient continues to have a NIS score ≥ 5 and ≤ 130≥ 5 and ≤ 130

Patient continues to have a KPS score ≥ 60%≥ 60%

Documentation that the patient has experienced a positive clinical response to Amvuttra or Onpattro (e.g., improved neurologic impairment, motor function, quality of life, slowing of disease progression, etc.)

Combination therapy exclusion (drug-specific)

For Amvuttra, patient is not receiving Amvuttra in combination with RNA interference agents or transthyretin stabilizers
For Onpattro, patient is not receiving Onpattro in combination with RNA interference agents or transthyretin stabilizers

Prescribed by or in consultation with a neurologist

Dosing is in accordance with the FDA prescribing information

Authorization is for no more than 12 months

Genetic testing showing a pathogenic TTR mutation (e.g., V30M) or cardiac/noncardiac tissue biopsy confirming ATTR amyloid deposits, or radionuclide imaging (99mTc-DPD, 99mTc-PYP, or 99mTc-HMDP) with grade 2–3 cardiac uptake and absence of AL amyloidosis
Baseline and ongoing PND (≤ IIIb), FAP Stage (1 or 2), NIS (≥5 and ≤130), and KPS (≥60%)
NYHA class (I, II, or III) and NT‑proBNP documentation; signs/symptoms of heart failure and history of ≥1 heart failure hospitalization
Documentation of positive clinical response for continuation (improved symptoms, QoL, slowed progression, decreased hospitalizations)

Billing Rule

Dosing per FDA label

Dosing must follow the FDA prescribing information and claim reimbursement follows applicable HCPCS J‑codes for the agents.

J0222
J0225

Denial Risk

Combination therapy exclusions

Claims may be denied if Amvuttra or Onpattro are used with specific disallowed agents. The policy prohibits concurrent use with other RNA interference agents and with transthyretin stabilizers; use in combination can lead to claim denial per the policy.

Disallowed RNAi agents: Onpattro (patisiran), Wainua (eplontersen), Tegsedi (inotersen)
Disallowed transthyretin stabilizers: Vyndaqel (tafamidis meglumine), Vyndamax (tafamidis), Attruby (acoramidis)
Implication: Claims for Amvuttra or Onpattro used in combination with these agents may be denied

08/15/2025editorial_correction

Corrected typographical error.

codes_added

Applicable codes section expanded to include ICD-10 diagnosis codes E85.0, E85.4, and E85.82 and lists HCPCS J0222 (patisiran 0.1 mg) and J0225 (vutrisiran 1 mg).